The long-term research goal of this laboratory is to develop and implement new, low-cost, minimally invasive, image-guided interventions for human diseases, in particular to improve outcomes in solid malignancies amenable to this approach such as breast or prostate cancer, metastatic colorectal cancer, lung cancer, and hepatocellular carcinoma (HCC), which is the focus of this application. Current methods such as radiofrequency ablation are inadequate with regard to treatable lesion size, tumor recurrence, survival benefit, procedural risk, and cost. The objective in this application is to establish in vivo feasibility of a new ablation method recently discovered called thermochemical ablation. This technique, when narrowly defined, overcomes these shortcomings by exploiting the considerable heat energy released as water is formed in acid-base reactions. The central hypothesis of this application is that thermochemical ablation can create an evenly distributed zone of coagulation in liver tissue without systemic toxicity. To establish feasibility and test this hypothesis two aims are outlined below: Aim 1: Quantify the size, shape, reproducibility, and temperature history of acute thermochemical coagulation zones measured by multiple correlated modalities based upon the known key variables of volume and concentration, with injection rates of acid and base constant. The eventual goal is treatment in humans where excision and pathologic correlation of tissues in most patients is not feasible. To address this, perfusion defects seen on CT scans of treated, explanted pig livers will be measured and correlated with three volume data sets: gross pathology, viability staining, and microscopic pathology. This will provide initial data for a robust imaging biomarker of the zone of coagulation created using the method. Aim 2: Characterize acute effects of thermochemical ablation at both tissue and systemic levels. Tissue effects will be visualized in selected sections from treated specimens using histologic methods to image necrosis and cell death. The microscopic appearance of the ablations will be characterized and the transition zone to normal tissue will be evaluated. Systemic effects are possible due to the use of concentrated solutions of acid and base that could potentially alter the whole animal physiology. Therefore serum osmolality, arterial blood gas measurements (pO2, pCO2, pH), and electrolytes will be monitored, with serial sampling after injection to detect changes.